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Faculty Detail    
Campus Address BBRB 366 Zip 2170
Phone 205-996-9282
E-mail saad@uab.edu
Other websites Lab

Undergraduate  Birzeit University, Ramallah, Palestine    1996  B.S 
Graduate  Bergen University, Bergen, Norway    1998  M.S 
Graduate  Emory University, Atlanta, GA    Ph.D  2002 

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Microbiology  Microbiology Assistant Professor
Center  Center for AIDS Research  Center for AIDS Research Assistant Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Assistant Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Assistant Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 

Biographical Sketch 
Obtained his B.S degree in Chemistry at Birzeit University in Palestine (1996), M.S degree in Bioinorganic Chemistry at Bergen University in Norway (1998; advisor: Dr. Einar Sletten), and a Ph.D degree in Bioinorganic Chemistry at Emory University in Atlanta (2002; advisor: Dr. Luigi Marzilli). His M.S. and Ph.D studies focused on studying the interactions of cisplatin, a leading anticancer drug, with DNA by using Nuclear Magnetic Resonance (NMR) and other biophysical methods. Dr. Saad's postdoctoral work in Dr. Michael Summers' lab (HHMI, UMBC) focused on the mechanism by which retroviruses are directed to specific cellular membranes for assembly. Dr. Saad joined the UAB faculty in 2007.

Society Memberships
Organization Name Position Held Org Link
A member of the American Association for the Advancement of Science (AAAS)  2006 – present   
A member of the American Chemical Society (ACS)  2002 – present    
A member of The American Society for Biochemistry and Molecular Biology (ASBMB) (ASBMB)  2011 – present    
A member of the American Society for Microbiology (ASM)  2010 – present    

Research/Clinical Interest
HIV-Host Interactions and Fas-Mediated Apoptosis
Structural Basis for HIV Gag interactions with Cellular Constituents: Human immunodeficiency virus type-1 (HIV-1), the causative agent of AIDS, is blamed for over 34 million deaths and is poised to claim over 2 million lives a year in the absence of efficient therapeutic intervention. HIV-1 replication is strongly dependent on the cellular machinery to produce progeny virus. Since its discovery, efforts have focused on the development of effective vaccines and drugs that target different stages of the HIV lifecycle. Combinations of drugs that target protease, reverse transcriptase, integrase or virus fusion form the basis of current antiretroviral therapy (ART). However, the genetic diversity and the ability of the virus to mutate to evade drug treatment remains a threat to the future success of ART. The discovery of cellular factors that participate in HIV-1 replication pathways has provided new insights into the molecular basis of virus–host cell interactions. Drugs that target the essential interactions of viral factors with host-proteins have the potential to not only complement current therapy, but may also overcome the problem of viral escape. As host-factors are stable and not diverse, the mutational capacity of the virus that usually allows for drug escape is thus restricted by the requirement to remain compatible to an invariant host-factor. Elucidation of the molecular interactions between the host cell and HIV are important for understanding the virus replication and the subsequent cytopathogenesis in the infected cell, which will aid in the development of more efficient antiviral drugs. We are interested in the underlying structural basis by which retroviral Gag polyproteins interact with cellular constituents during the virus replication cycle. A major component of our research is directed towards understanding key protein-protein and protein-membrane interactions that are critical for HIV assembly. We employ a set of biochemical, biophysical and structural biology tools to identify the molecular mechanisms governing HIV-1 Gag intracellular trafficking and subsequent assembly on the plasma membrane. Another aspect of our research is to identify small molecule inhibitors that are able to block virus-host protein-protein complexes and ultimately serve as potential anti HIV drugs. The results generated from this research will provide new insights into these mechanisms and identify new attractive targets that will ultimately aid in rational drug design. Structural Basis of Fas-mediated Apoptosis and Mechanism of Inhibition: Cholangiocarcinoma is the second most common primary malignant tumor of the liver and comprises approximately 20% of all hepatobiliary malignancies in the United States. In the last decade, a marked increase in the incidence and mortality from cholangiocarcinoma necessitates an effective search for a therapy regimen. Apoptosis is a strictly regulated process by which abnormal cells are removed from the body without altering the immune system or generating an inflammatory response. Inappropriate apoptosis (enhanced or diminished) is linked to many human diseases including neurodegenerative and autoimmune disorders, AIDS, and many types of cancers. Cells from a wide variety of human malignancies show a decreased ability to undergo apoptosis in response to various stimuli, which may contribute to the clonal expansion of cancer cells. The apoptotic pathway is normally initiated by cell surface death receptors, which belong to a Tumor Necrosis Factor (TNF) super family of receptors. The cytoplasmic regions of two major receptors, Fas and TNF-receptor-1 (TNF-R1), share a homologous cytoplasmic region of ~80 amino acids called the death domain (DD). These receptors undergo a conformational change in response to their cognate ligands, allowing them to interact with adaptor proteins such as Fas-associated death domain (FADD). Engagement of Fas by Fas ligand (FasL) initiates a cascade of interactions that lead to activation of specific proteases called caspases (Cysteine ASPartyl-specific proteASES). Fas-FasL interaction leads to activation of caspase 8 (by FADD) and formation of death-inducing signaling complex (DISC). Active caspase 8 then cleaves and activates caspases 3, 6, and 7, which target cellular substrates and ultimately lead to cell death. DISC formation and subsequent protein recruitment is a critical initial step in regulating Fas-mediated apoptosis. There is compelling evidence that Fas interacts with various molecules, suggesting that Fas signaling is complex and regulated by multiple proteins. Among these is calmodulin (CaM), which is recruited into DISC in cholangiocarcinoma cells. It has been hypothesized that Fas-CaM interaction may affect Fas-FADD interaction and thus regulates DISC assembly and inhibits apoptosis in cholangiocarcinoma cells. Thus, Fas-CaM interaction appears to be an inhibitory component of DISC and may play a vital role in obstruction of caspases activation. Our lab is interested in understanding the structural determinants of Fas-CaM interaction, which will be critical to understanding the precise molecular mechanism of Fas-mediated apoptosis and mechanism of inhibition. These studies will likely lead to developing new strategies to develop inhibitors of these interactions and thus to cancer treatment.

Selected Publications 
Publication PUBMEDID
Jiri Vlach and Jamil S. Saad (2013). “Trio Engagement via Plasma Membrane Phospholipids and the Myristoyl Moiety Governs HIV-1 MA Binding to Bilayers”, Proc. Natl. Acad. Sci. USA, 110, 3525-3530.  23401539 
Juan Calix, Jamil S. Saad, Alison Brady, Moon Nahm (2012). ‘Structural Characterization of Streptococcus pneumonia serotype 9A Capsule Polysaccharide Reveals the Role of the Glycosyl 6-O-acetyltransferase wcjE’ in Serotype 9V Capsule Biosynthesis and Immunogenicity”, J. Biol. Chem, 287, 13996-14003.  22367197 
Ruba H. Ghanam, Alexandra B. Samal, Timothy F. Fernandez, Jamil S. Saad (2012). “Role of the HIV-1 Matrix Protein in Gag Intracellular Trafficking and Targeting to the Plasma Membrane for Virus Assembly”. Invited Review in Frontiers in Microbiology, 3, 55.  22363329 
Altaira D. Dearborn, Michael S. Spilman, Priyadarshan K. Damle, Jenny R. Chang, Eric B. Monroe, Jamil S. Saad, Gail E. Christie and Terje Dokland (2011) “The Staphylococcus aureus pathogenicity island 1 protein gp6 functions as an internal scaffold during capsid size determination”, J. Mol. Biol., 412, 710-722.  21821042 
Jamil S. Saad, Patricia A. Marzilli, Francesco P. Intini, Giovanni Natile, and Luigi G. Marzilli (2011) “Single-stranded Oligonucleotide Adducts Formed by Pt Complexes Favoring Left-handed Base Canting. Steric Effect of Flanking Residues and Relevance to DNA Adducts Formed by Pt Anticancer Drugs”. Inorg. Chem., 50, 8608-8620.  21819051 
Alexandra B. Samal, Ruba H. Ghanam, Timothy F. Fernandez, Eric B. Monroe and Jamil S. Saad (2011). “NMR, Biophysical and Biochemical Studies Reveal the Minimal Calmodulin-Binding Domain of the HIV-1 Matrix Protein”. J. Biol. Chem., 286, 33533-33543.  21799007 
Jamil S. Saad, Michele Benedetti, Giovanni Natile, and Luigi G. Marzilli (2011). “NMR Studies of Models Having the Pt(d(GpG)) 17-Membered Macrocyclic Ring Formed in DNA by Platinum Anticancer Drugs. Pt Complexes with Bulky Chiral Diamine Ligands”, Inorg. Chem., 50, 4559-4571.  21510625 
Ruba H. Ghanam, Timothy Fernandez, Emily Fledderman, and Jamil S. Saad (2010) “Binding of Calmodulin to the HIV-1 Matrix Protein Triggers Myristate Exposure”. J. Biol. Chem., 285, 41911-41920.  20956522 
Emily L. Fledderman, Ken Fujii, Ruba H. Ghanam, Kayoko Waki, Peter E. Prevelige, Eric O. Freed, and Jamil S. Saad (2010) “Myristate Exposure in the HIV-1 Matrix Protein is Modulated by pH”. Biochemistry, 49, 9551-9562.  20886905 
Kathleen G. Valentine, Ronald Peterson, Jamil S. Saad, Michael F. Summers, Xianzhong Xu, James B. Ames, and A. Joshua Wand (2010). “Reverse micelle encapsulation of membrane anchored proteins for solution NMR studies”. Structure, 18, 9-16.  20152148 
Hamard-Peron, E., Juilliard, F., Jamil S. Saad, Roy, C., Roingeard, P., Michael F. Summers, Darlix, JL., Picart, C. and D. Muriaux (2010). “Targeting of MuLV Gag to the Plasma Membrane is Mediated by PI(4,5)P2/PS and a polybasic region in the Matrix. J. Virol, 84, 503-515.  19828619 
Jamil S. Saad, Giovanni Natile, and Luigi G. Marzilli (2009) “Origins of the Distortions in the Base Pair Step Adjacent to Platinum Anticancer Drug-DNA Adducts. Fundamental NMR Solution Studies Utilizing Right-Handed Cross-Link Models Having 5'- and 3'-Flanking Residues”, J. Am. Chem. Soc., ”, 131, 12314-12324.  19655752 
Jamil S. Saad, Sherimay D. Ablan, Ruba H. Ghanam, Andrew Kim, Kalola Andrews, Kunio Nagashima, Eric O. Freed, and Michael F. Summers (2008). “Structure of the myristylated HIV-2 MA protein and the role of PI(4,5)P2 in membrane targeting”, J. Mol. Biol., 382, 434-347.  18657545 
Jamil S. Saad, Erin Loeliger, Paz Luncsford, Mellisa Liriano, Janet Tai, Andrew Kim, Jaime Miller, Anjali Joshi, Eric O. Freed and Michael F. Summers (2007). “Point Mutations in the HIV-1 Matrix Protein Turn off the Myristyl Switch”, J. Mol. Biol., 366, 574-585 (Illustrated on the cover).  17188710 
Jamil S. Saad, Jaime Miller, Janet Tai, Andrew Kim, Ruba H. Ghanam, and Michael F. Summers. (2006) “Structural Basis for Targeting HIV-1 Gag proteins to the Plasma Membrane for Virus Assembly”, Proc. Natl. Acad. Sci. USA, 103, 11364-11369 (Highlighted on the cover).  16840558 

HIV, Gag, NMR, Cancer, Drug design